The long term objectives of this program are: (1) to determine the conditions under which initial deposition of sodium urate cystals occurs, leading to gouty arthritis, and (2) to find drugs and/or treatments to inhibit sodium urate crystallization in hyperuricemic individuals. Previous research at USC has shown that urate crystallization is strongly stimulated by calcium ion and by hydrogen ion. Preliminary experiments also demonstrated considerable patient-to-patient variation in the influence of synovial fluid on crystallization under laboratory conditions, with fluid from rheumatoid patients inhibiting crystallization. The proposed research consists of two parts: (1) Gathering and characterization of suitable physiological specimens, such as synovial fluids. Particular attention will be paid to the total and free calcium ion concentrations. Synovial fluids will be fractionated. (2) Study the influence of the foregoing substances and of selected drugs on initiation (nucleation) of crystallization at 37 degrees C. Substances will be added to supersaturated solution that would not otherwise nucleate. Crystallization will be detected by examining samples in the polarizing microscope and by analysis of filtered samples for urate concentration. The solution urate concentration may be gradually increased by dialysis.